The present invention relates to the use of hydroxyphenylvinylthiazoles in the antimicrobial treatment of surfaces, as an antimicrobial active ingredient against gram-positive and gram-negative bacteria, yeasts and fungi, as well as in the preservation of cosmetics, household products, textiles, plastics and disinfectants.
The hydroxyphenylvinylthiazoles used according to the invention have the formula 
R1, R2, R3 and R4 are each independently of the others hydrogen; halogen; hydroxy, C1-C16-alkyl, C1-C16alkoxy, phenyl; phenyl-C1-C3alkyl; C6-C10aryloxy, amino, mono-C1-C5alkyl-amino, di-C1-C5alkylamino or -NO2; wherein at least one of the radicals R1, R2, R3 and R4 is hydroxy;
R5 is C1-C5alkyl; C1-C5alkoxy; or unsubstituted or halo-, C1-C5alkyl-, C1-C5alkoxy-, hydroxy- or pyrrolidinyl-substituted phenyl.
C1-C16Alkyl radicals are straight-chain or branched alkyl radicals, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, un-decyl, dodecyl, tetradecyl, pentadecyl or hexadecyl.
C1-C16Alkoxy is, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy or pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy, undecyloxy, do decyloxy, tetradecyloxy, pentadecyloxy or hexadecyloxy.
Halogen is fluorine, chlorine, bromine or iodine.
The hydroxyphenylvinylthiazoles used according to the invention may be in the form of E or Z isomers. They are preferably in the form of E isomers.
Compounds that are of interest are hydroxyphenylvinylthiazoles of formula (1) wherein
R1, R2, R3 and R4 are each independently of the others hydrogen, hydroxy, C1-C5alkyl, C1-C5-alkoxy or phenyl-C1-C3alkyl.
Also of interest are compounds of formula (1) wherein
R5 is C1-C5alkyl; or unsubstituted or halo- or pyrrolidinyl-substituted phenyl.
Compounds that are of very special interest have the formula 
Further hydroxyphenylvinylthiazoles according to the invention are listed by way of example in Table 1 below:
The preparation of the hydroxyphenylvinylthiazoles used according to the invention is pre-ferably carried out in a solid-phase synthesis using a trityl resin. The preparation is carried out according to the following scheme: 
In the above scheme, R1, R2, R3, R4 and R5 are as defined for formula (1).
The method of synthesis is based on that specified in the literature by R1 Willard et al., Chemistry and Biology, 2, 1995, 45-51. The preparation process according to the invention differs in that a trityl resin is used and the method of loading the resin is different.
Further details regarding the preparation process according to the invention will be found in the corresponding Examples.
The thiazol-2-ylmethylphosphonates (compound of formula (1c)) used as starting materials in the preparation according to the invention are prepared according to the known Hantzsch thiazole synthesis: 
Diethyl (2-amino-2-thioxoethyl)phosphonate (2.1 g; 10 mmol) and bromomethyl ketone (10.5 mmol) are dissolved in methanol (10 ml) under a protective gas atmosphere. The reaction mixture is subsequently heated for 5 hours under reflux and then concentrated to dryness. The residue is taken up in dichloromethane (100 ml) and washed with saturated aqueous NaHCO3 solution (2xc3x9750 ml) and NaCl solution (50 ml). The washing solutions are extracted with dichloromethane (25 ml) and the combined organic extracts are concentrated to dry-ness.
Yields: R2=4-F-Ph (87.1%); R2=t. but (84.7%); R2=4-(pyrrolidin-1-yl)-phenyl (98%); R2=Et (86.2%); R2=Ph (100%).
All the compounds are characterised by 1H-NMR and show the corresponding chemical shifts.
The hydroxyphenylvinylthiazoles used according to the invention exhibit a pronounced anti-microbial action, especially against pathogenic gram-positive and gram-negative bacteria and also against bacteria of skin flora and, additionally, against yeasts and moulds. Accordingly, they are especially suitable in the disinfection, deodorisation and also the general and antimicrobial treatment of the skin and mucosa and of integumentary appendages (hair), more especially in the disinfection of the hands and of wounds.
Accordingly, they are suitable as antimicrobial active ingredients and preservatives in personal care preparations, for example shampoos, bath additives, hair-care products, liquid and solid soaps (based on synthetic surfactants and salts of saturated and/or unsaturated fatty acids), lotions and creams, deodorants, other aqueous or alcoholic solutions, for example cleansing solutions for the skin, moist cleansing cloths, oils or powders.
Accordingly, the invention relates also to a personal care preparation comprising at least one compound of formula (1), and cosmetically tolerable carriers or adjuvants.
The personal care preparation according to the invention comprises from 0.01 to 15% by weight, preferably from 0.1 to 10% by weight, based on the total weight of the composition, of a hydroxyphenylvinylthiazole compound of formula (1), and cosmetically tolerable adjuvants.
Depending on the form of the personal care preparation, it comprises further components in addition to the hydroxyphenylvinylthiazole compound of formula (1), for example sequestering agents, colourants, perfume oils, thickeners or strengthening agents (consistency regulators), emollients, UV absorbers, skin-protecting agents, antioxidants, additives that improve the mechanical properties, such as dicarboxylic acids and/or Al, Zn, Ca, Mg salts of C14-C22 fatty acids, and optionally preservatives.
The personal care preparation according to the invention may be formulated as a water-in-oil or oil-in-water emulsion, as an alcoholic or alcohol-containing formulation, as a vesicular dispersion of an ionic or non-ionic amphiphilic lipid, as a gel, as a solid stick or as an aerosol formulation.
In the case of a water-in-oil or oil-in-water emulsion, the cosmetically tolerable adjuvant contains preferably from 5 to 50% of an oily phase, from 5 to 20% of an emulsifier and from 30 to 90% water. The oily phase may contain any oil suitable for cosmetic formulations, e.g. one or more hydrocarbon oils, a wax, a natural oil, a silicone oil, a fatty acid ester or a fatty alcohol. Preferred mono- or poly-ols are ethanol, isopropanol, propylene glycol, hexylene glycol, glycerol and sorbitol.
Cosmetic formulations according to the invention are used in a variety of fields. Especially the following preparations, for example, come into consideration:
skin-care preparations, e.g. skin-washing and cleansing preparations in the form of tablet-form or liquid soaps, soapless detergents or washing pastes;
bath preparations, e.g. liquid (foam baths, milks, shower preparations) or solid bath preparations, e.g. bath cubes and bath salts;
skin-care preparations, e.g. skin emulsions, multi-emulsions or skin oils;
cosmetic personal care preparations, e.g. facial make-up in the form of day creams or powder creams, face powder (loose and pressed), rouge or cream make-up, eye-care preparations, e.g. eyeshadow preparations, mascara, eyeliner, eye creams or eye-fix creams; lip-care preparations, e.g. lipsticks, lip gloss, lip contour pencils, nail-care preparations, such as nail varnish, nail varnish removers, nail hardeners or cuticle removers;
intimate hygiene preparations, e.g. intimate washing lotions or intimate sprays;
foot-care preparations, e.g. foot baths, foot powders, foot creams or foot balsams, special deodorants and antiperspirants or callus-removing preparations;
light-protective preparations, such as sun milks, lotions, creams and oils, sun blocks or tropicals, pre-tanning preparations or after-sun preparations;
skin-tanning preparations, e.g. self-tanning creams;
depigmenting preparations, e.g. preparations for bleaching the skin or skin-lightening preparations;
insect-repellents, e.g. insect-repellent oils, lotions, sprays or sticks;
deodorants, such as deodorant sprays, pump-action sprays, deodorant gels, sticks or roll-ons;
antiperspirants, e.g. antiperspirant sticks, creams or roll-ons;
preparations for cleansing and caring for blemished skin, e.g. soapless detergents (solid or liquid), peeling or scrub preparations or peeling masks;
hair-removal preparations in chemical form (depilation), e.g. hair-removing powders, liquid hair-removing preparations, cream- or paste-form hair-removing preparations, hair-removing preparations in gel form or aerosol foams;
shaving preparations, e.g. shaving soap, foaming shaving creams, non-foaming shaving creams, foams and gels, preshave preparations for dry shaving, aftershaves or after-shave lotions;
fragrance preparations, e.g. fragrances (eau de Cologne, eau de toilette, eau de parfum, parfum de toilette, perfume), perfume oils or cream perfumes;
dental-care, denture-care and mouth-care preparations, e.g. toothpastes, gel toothpastes, tooth powders, mouthwash concentrates, anti-plaque mouthwashes, denture cleaners or denture fixatives;
cosmetic hair-treatment preparations, e.g. hair-washing preparations in the form of shampoos and conditioners, hair-care preparations, e.g. pretreatment preparations, hair tonics, styling creams, styling gels, pomades, hair rinses, treatment packs, intensive hair treatments, hair-structuring preparations, e.g. hair-waving preparations for permanent waves (hot wave, mild wave, cold wave), hair-straightening preparations, liquid hair-setting preparations, hair foams, hairsprays, bleaching preparations, e.g. hydrogen peroxide solutions, lightening shampoos, bleaching creams, bleaching powders, bleaching pastes or oils, temporary, semi-permanent or permanent hair colourants, preparations containing self-oxidising dyes, or natural hair colourants, such as henna or camomile.
An antimicrobial soap has, for example, the following composition:
0.01 to 5% by weight compound of formula (1)
0.3 to 1% by weight titanium dioxide
1 to 10% by weight stearic acid and
ad 100% soap base, e.g. the sodium salts of tallow fatty acid and coconut fatty acid or glycerol.
A shampoo has, for example, the following composition:
0.01 to 5% by weight compound of formula (1)
12.0% by weight sodium laureth-2-sulfate
4.0% by weight cocamidopropyl betaine
3.0% by weight NaCl and
water ad 100%.
A deodorant has, for example, the following composition:
0.01 to 5% by weight compound of formula (1)
60% by weight ethanol
0.3% by weight perfume oil and
water ad 100%.